多发性骨髓瘤达雷妥尤单抗治疗效果及预后影响因素分析

Analysis of efficacy and prognostic influencing factors of daratumumab in treatment of multiple myeloma

目的探讨含达雷妥尤单抗方案治疗多发性骨髓瘤(MM)的临床疗效及影响患者无进展生存(PFS)的相关因素。方法回顾性病例系列研究。收集2021年1月至2023年9月长治医学院附属和平医院收治的接受含达雷妥尤单抗方案治疗的21例MM患者临床资料。患者均接受达雷妥尤单抗(16 mg/kg静脉滴注)联合其他药物治疗,28 d为1个周期,直至疾病进展。21例中,初诊多发性骨髓瘤(NDMM)6例,复发难治多发性骨髓瘤(RRMM)7例,初治时VRD(硼替佐米+来那度胺+地塞米松)方案治疗效果差而采用达雷妥尤单抗二线治疗8例(达雷妥尤单抗二线治疗组)。总结患者达雷妥尤单抗治疗2个周期后疗效;采用Kaplan-Meier法分析全组及NDMM、RRMM患者PFS,组间比较采用log-rank检验;将疾病不同状态及性别、年龄纳入单因素和多因素Cox比例风险模型,筛选影响MM患者PFS的因素。结果21例患者中位年龄[M(Q1,Q3)]62岁(55岁,68岁);男性17例,女性4例。达雷妥尤单抗治疗2个周期后,全组总缓解率(ORR)为85.7%(18/21),其中,2例(9.5%)达严格意义的完全缓解(sCR),3例(14.3%)达完全缓解(CR),9例(42.9%)达非常好的部分缓解(VGPR),4例(19.0%)达部分缓解(PR),2例(9.5%)疾病稳定,1例(4.8%)疾病进展。达雷妥尤单抗治疗2个周期后,6例NDMM患者均缓解,其中2例达sCR,1例达CR,3例达VGPR;7例RRMM患者中4例缓解,其中1例达CR,3例达PR;8例达雷妥尤单抗二线治疗患者均缓解,其中1例达CR,6例达VGPR,1例达PR;3组间ORR差异有统计学意义(P=0.010),NDMM与达雷妥尤单抗二线治疗患者间ORR差异无统计学意义(P=0.245),NDMM患者ORR高于RRMM患者,差异有统计学意义(P=0.029)。中位随访时间为15.4个月(95%CI:13.7~17.1个月)。全组中位PFS时间为10.6个月(95%CI:7.3~15.5个月);NDMM患者中位PFS时间未达到,RRMM患者中位PFS时间为14.6个月(95%CI:2.1~27.2个月),达雷妥尤单抗二线治疗患者的中位PFS时间为9.6个月(95%CI:9.5~9.7个月),3组间PFS差异无统计学意义(P=0.085)。多因素Cox回归分析显示,年龄高为MM患者PFS的独立危险因素(HR=1.12,95%CI:1.03~1.21,P=0.009)。结论达雷妥尤单抗治疗MM有较好的效果,可作为NDMM患者的一线治疗方案,可提高既往VRD方案治疗效果不佳MM患者的缓解率,也可能改善RRMM患者预后。年龄高可能为接受达雷妥尤单抗治疗的MM患者疾病进展的危险因素。

Objective:To investigate the clinical efficacy of daratumumab-containing regimen in the treatment of multiple myeloma(MM)and the associated factors affecting patients'progression-free survival(PFS).Methods:A retrospective case series study was conducted.Clinical data of 21 MM patients who were treated with daratumumab-containing regimen in the Heping Hospital Affiliated to Changzhi Medical College from January 2021 to September 2023 were collected.The patients were treated with daratumumab(16 mg/kg intravenous drip)combined with other drugs for 28 d as 1 cycle until disease progression.Among the 21 cases,6 cases were newly diagnosed multiple myeloma(NDMM),7 cases were relapsed/refractory multiple myeloma(RRMM),and 8 cases were second-line treatment with daratumumab after the poor outcome of VRD(bortezomib+lenalidomide+dexamethasone)regimen at the time of initial treatment(daratumumab second-line treatment group).The efficacy of the patients after 2 cycles of daratumumab treatment was summarized;the PFS of the whole group and the NDMM and RRMM patients was analyzed by using Kaplan-Meier method,and log-rank test was used for comparison between the groups;the different status of disease,gender and age were included in the univariate and multivariate Cox proportional hazards models to screen the factors affecting the PFS of MM patients.Results:The median age[M(Q1,Q3)]of 21 patients was 62 years old(55 years old,68 years old);17 were male and 4 were female.After 2 cycles of daratumumab treatment,the overall remission rate(ORR)of the whole group was 85.7%(18/21),2 cases(9.5%)achieved strict complete remission(sCR),3 cases(14.3%)achieved complete remission(CR),9 cases(42.9%)achieved very good partial remission(VGPR),4 cases(19.0%)achieved partial remission(PR),2 cases(9.5%)had stable disease and 1 case(4.8%)had disease progression.After 2 cycles of daratumumab treatment,all 6 NDMM patients were in remission,with 2 cases of sCR,1 case of CR,and 3 cases of VGPR;4 of 7 RRMM patients were in remission,with 1 case of CR and 3 cases of PR;8 patients with daratumumab second-line treatment were in remission,with 1 case of CR,6 cases of VGPR,and 1 case of PR;the difference in ORR among the 3 groups was statistically significant(P=0.010),the difference in ORR between patients with NDMM and daratumumab second-line treatment was not statistically significant(P=0.245),the ORR of NDMM patients was higher than that of RRMM patients,and the difference was statistically significant(P=0.029).The median follow-up time was 15.4 months(95%CI:13.7-17.1 months).The median PFS time for the whole group was 10.6 months(95%CI:7.3-15.5 months);the median PFS time was not reached in NDMM patients,the median PFS time was 14.6 months(95%CI:2.1-27.2 months)in RRMM patients,the median PFS time was 9.6 months(95%CI:9.5-9.7 months)in patients with daratumumab second-line treatment,and the difference in PFS among the 3 groups was not statistically significant(P=0.085).Multivariate Cox regression analysis showed that high age was an independent risk factor for PFS in MM patients(HR=1.12,95%CI:1.03-1.21,P=0.009).Conclusions:Daratumumab has good results in treating MM and can be used as a first-line treatment option for NDMM patients,which may improve the remission rate of MM patients with previous ineffective treatment of VRD regimen,and may also improve the prognosis of RRMM patients.High age may be a risk factor for disease progression in MM patients treated with daratumumab.